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Molekulare Pathologie des kolorektalen Karzinoms

Molecular pathology of colorectal cancer

  • Pathologie
  • Published:
Wiener klinisches Magazin Aims and scope

Zusammenfassung

In den letzten Jahren konnten beim kolorektalen Karzinom (KRK) mehrere prädiktive und prognostische Biomarker etabliert werden. Der RAS-Mutationsstatus ist ein in der täglichen Routine breit angewendeter prädiktiver Biomarker für eine Therapie mit Epidermal-Growth-Factor-Receptor(EGFR)-Inhibitoren. Eine BRAF-Mutation besitzt in diesem Kontext hingegen keine prädiktive Aussagekraft. Der Nachweis einer hochgradigen Mikrosatelliteninstabilität (MSI-H) ist prädiktiv für das Ansprechen auf eine 5-Fluoruracil-Monotherapie. Prognostische Biomarker beim KRK sind der MSI-Status sowie der Nachweis einer BRAF-Mutation. Nach der aktuellen WHO-Klassifikation werden wenig und undifferenzierte KRK sowie MSI-assoziierte morphologische Sonderformen anhand des MSI-Status molekular graduiert. Der Nachweis einer BRAF-Mutation vor dem Hintergrund einer Mikrosatellitenstabilität (MSS) ist mit einer sehr schlechten Prognose assoziiert und stellt somit den aggressivsten molekularen Subtyp des KRK dar. Für die Abklärung eines begründeten Verdachts auf eine Assoziation eines KRK mit einem hereditären nichtpolipösen kolorektalen Karzinom (HNPCC-Syndrom) wird aktuell eine immunhistochemische und molekularpathologische Stufendiagnostik empfohlen.

Abstract

In recent years, several predictive and prognostic biomarkers have been established in colorectal cancer (CRC). The RAS-mutation status is widely applied in the daily routine diagnostic as predictive biomarker for treatment with EGFR-inhibitors. A BRAF- mutation has no predictive value in this context. The detection of high-grade microsatellite instability (MSI-H) is a predictive biomarker for response to 5-Fluoruracil-monotherapy. Prognostic biomarkers in CRC are the MSI-status and the mutational status of BRAF. According to the current WHO classification poorly and undifferentiated CRC and MSI-associated special morphological subtypes are molecular graded depending on their MSI-status. The detection of a BRAF-mutation in the context of microsatellite stability (MSS) is associated with a very poor prognosis and thus represents the most aggressive molecular subtype of CRC. In patients with positive Bethesda criteria a stepwise immunohistochemical and molecular diagnostic scheme is proposed.

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Authors and Affiliations

  1. Pathologisches Institut, Ludwig-Maximilians-Universität München, Thalkirchner Straße 36, 80337, München, Deutschland

    Jens H.L. Neumann, Andreas Jung & Thomas Kirchner

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  1. Jens H.L. Neumann
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  2. Andreas Jung
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  3. Thomas Kirchner
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Correspondence to Jens H.L. Neumann.

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Erklärung zum Interessenkonflikt

T.Kirchner gibt finanzielle Verbindungen zu AMGEN, Merck-Sorono und Roche Diagnostics an. A. Jung gibt finanzielle Verbindungen zu AMGEN und Merck-Sorono an. J. Neumann gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag enthält keine Studien an Menschen oder Tieren.

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Dieser Beitrag wurde in der Zeitschrift Der Pathologie 2015 · 36:137–144. DOI 10.1007/s00292-015-0005-3 erstveröffentlicht. Zweitpublikation mit freundlicher Genehmigung des Autors.

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Neumann, J., Jung, A. & Kirchner, T. Molekulare Pathologie des kolorektalen Karzinoms. Wien klin Mag 18, 140–148 (2015). https://doi.org/10.1007/s00740-015-0061-6

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